Lazertinib

Lazertinib is a prescription medication indicated in combination with amivantamab for first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.

• Lazertinib is available under the following different brand names: Lazcluze.

Common side effects of Lazertinib include:

• rash 
• feeling very tired
• infected skin around the nail  
• diarrhea
• infusion-related reaction (amivantamab) 
• constipation
• muscle and joint pain 
• COVID-19
• sores in the mouth 
• bleeding
• swelling of hands, ankles, feet, face, or entire body
• decreased appetite
• unusual feeling in the skin (such as tingling or crawling) 
• nausea
• changes in certain blood tests
• itchy skin

Serious side effects of Lazertinib include:

• blood clot problems
• lung problems
• skin problems
• eye problems

Rare side effects of Lazertinib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 80 mg
• 240 mg

NSCLC

Adult dosage

• 240 mg orally once a day plus amivantamab (dose based on baseline body weight) until disease progression or unacceptable toxicity
• Amivantamab dosing for weight less than 80 kg
• Week 1, Day 1: 350 mg IV x 1 dose
• Week 1, Day 2: 700 mg IV x 1 dose
• Weeks 2-5: 1,050 mg IV weekly
• Week 6: No dose
• Week 7 and thereafter: 1,050 mg IV every 2 weeks

Amivantamab dosing for weight greater than or equal to 80 kg

• Week 1, Day 1: 350 mg IV x 1 dose
• Week 1, Day 2: 1,050 mg IV x 1 dose
• Weeks 2-5: 1,400 mg IV weekly
• Week 6: No dose
• Week 7 and thereafter: 1,400 mg IV every 2 weeks

Administer Lazertinib before amivantamab when given on the same day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Lazertinib has no noted severe interactions with any other drugs
• Lazertinib has no noted serious interactions with any other drugs
• Lazertinib has no noted moderate interactions with any other drugs
• Lazertinib has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Lazertinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Lazertinib?”

Cautions

• Venous thromboembolic events (VTE)
• Serious and fatal VTE (e.g., deep venous thrombosis [DVT] and pulmonary embolism [PE]) reported
• Median time to VTE onset: 84 days (range, 6-777)
• Administer prophylactic anticoagulation for the first 4 months of treatment; consider discontinuation if no signs or symptoms of VTE in the first 4 months
• Use of vitamin K antagonists is not recommended
• Monitor for signs and symptoms of VTE and treat as medically appropriate
• Hold, reduce dose, or discontinue lazertinib and amivantamab based on severity
• Interstitial lung disease (ILD)/pneumonitis
  • ILD/pneumonitis can occur; fatal cases reported
  • Monitor patients for new or worsening symptoms
  • Hold or discontinue as appropriate if ILD/pneumonitis is suspected or confirmed
• Dermatologic toxicity
  • Severe rash (e.g., dermatitis acneiform, pruritus, dry skin) reported
  • Median time to rash onset: 14 days (range: 1-556)
  • Apply alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream and limit sun exposure during and for 2 months after treatment
  • Wear protective clothing, use broad-spectrum UVA/UVB sunscreen, and consider other prophylactic measures (e.g., use of oral antibiotics) to reduce the risk of dermatologic toxicity
  • Start appropriate supportive care if toxicity develops (e.g., topical corticosteroids and topical and/or oral antibiotics)
  • Hold, reduce dose, or discontinue lazertinib and amivantamab based on severity
  • Promptly consult with or refer patient to a dermatologist for severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks
• Ocular toxicity
  • Ocular toxicity (.eg, keratitis) can occur
  • Promptly refer the patient to an ophthalmologist for new or worsening eye symptoms
  • Hold, reduce dose, or discontinue lazertinib and amivantamab based on severity
• Embryo-fetal toxicity
  • Fetal harm may occur if used during pregnancy
  • Advise pregnant patients of potential risk to the fetus
  • Effective contraception is recommended during and after therapy in women of reproductive potential and males with partners of reproductive potential
• Drug interaction overview
  • Lazertinib is a CYP3A4 substrate, a weak CYP3A4 inhibitor, and a BCRP inhibitor
  • Coadministration with strong and moderate CYP3A4 inducers
    • Avoid
    • May decrease lazertinib exposure and reduce efficacy
    • Consider alternant therapy that does not induce CYP3A4
  • Coadministration with certain CYP3A4 substrates
    • Lazertinib may increase concentrations of CYP3A4 substrates where minimal concentration changes may lead to serious adverse reactions
    • Follow recommendations for CYP3A4 substrates that interact with weak 3A4 inhibitors
    • Monitor CYP3A4 substrate for adverse reactions
  • Coadministration with BCRP substrates
    • Lazertinib may increase concentrations of BCRP substrates
    • Follow the recommendation for BCRP substrates
    • Monitor BCRP substrate for adverse reactions

Pregnancy and Lactation

• May cause fetal harm if administered to pregnant women, based on mechanism of action and animal studies
• Data are not available in pregnant women to evaluate for drug-associated risk
• Advise pregnant patients of potential risk to a fetus
• Perform pregnancy testing before initiation in females of reproductive potential
• Contraception
  • Effective contraception is recommended during therapy and for 3 weeks after the last dose in females of reproductive potential and males with women partners of reproductive potential
• Infertility
  • Fertility may be impaired in males and females, based on findings in animals
  • Effects reversible in females; effects on male testes in animal studies not reversible within a 2-week recovery period
• Lactation
  • Data are unavailable on the presence of the drug  in human milk, its effects on breastfed children or milk production
  • Avoid breastfeeding during therapy and for 3 weeks after the last dose due to the risk of serious adverse effects in nursing children